Updates of the MWS have finetuned the perceived risk. The MWS website says there is an increased cancer risk of 30 per cent in oestrogen-only treatment, and a two-fold risk in oestrogen-progestogen therapy, compared with women who do not take these drugs.

The risk increases the longer a woman uses HRT, but drops to normal level within five years after stopping use, the MWS says.

Biased

"HRT may or may not increase the risk of breast cancer, but the MWS did not establish that it does," the paper's authors write.

Among half a dozen points, the authors say cancers detected within a few months of the study's start would have already been present when the women were enrolled.

But these cases were not stripped out of the cancer count, they write.

The review also points to "detection bias" through the choice of participants.

The volunteers were taking part in a breast screening program when they were invited to join the study.

They would thus have already known about breast lumps and suspect lesions that point to breast cancer. As a result, the MWS found a 40 per cent higher incidence of breast cancer among its volunteers, regardless of whether they used hormone therapy or not, than in the population at large.

The paper also notes that breast cancers typically take many years to develop. It was thus "biologically implausible" that so many would have cropped up within a year or two of enrolment in the study, as the MWS maintained.

"The name 'Million Women Study' implies an authority beyond criticism or refutation," write the authors, led by Dr Samuel Shapiro, a professor of public health at the University of Cape Town, South Africa.

"Yet the validity of any study is dependent on the quality of its design, execution, analysis and interpretation. Size alone does not guarantee that the findings are reliable."

Standing by study

The leaders of the MWS rebut the criticism, saying that more than 20 studies had replicated its findings and a decline in the use of HRT had led to a fall in cases of breast cancer.

"Hormone-sensitive cancers are still three times as common in HRT users as in non-users or ex-users," said Dr Richard Peto, a professor of statistics and epidemiology at Oxford University.

Independent commentator Dr Anne Gombel, a French professor who is a member of the International Menopause Society, says a complex picture about breast cancer was emerging.

Breast density, alcohol and obesity, and not just HRT are now emerging as risk factors that should be taken into account, says Gombel.

"HRT does not carry the same risk and benefit for each woman; some women will have increased risks, some will have only benefits, and this also applies to breast cancer."

Debate over review

Dr Ian Fraser, a Professor in Reproductive Medicine at the University of Sydney says the critique is long overdue.

"[It] is an important contribution to the ongoing debate on the well-recognised benefits of hormone replacement therapy contrasted with a small number of uncertain disadvantages," says Fraser.

"Women need clear, balanced, accurate and unemotional information about the quality of published scientific recommendations. MWS failed to do this, and the current article goes a long way to remedying this."

But Professor Dame Valerie Beral, Director of the Cancer Epidemiology Unit, University of Oxford, dismisses the new study and questions the authors links to HRT.

"This paper is a re-statement of views held by many consultants to HRT manufacturers (as these authors are) attempting to dispute evidence about the adverse effects of HRT," says Beral.

"The authors omit to say that the MWS findings ... have been replicated in over 20 other studies. The totality of the worldwide evidence is now overwhelming."

"In line with the findings from these studies, the recent large decrease in HRT use has been followed in many countries by a nationwide decline in the incidence of breast cancer."